Hibma Jody C, Neufeld Daniel A, Halaby Marie-Jo, Yang Da-Qing
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota 57069, USA.
Anat Rec (Hoboken). 2007 Mar;290(3):243-50. doi: 10.1002/ar.20425.
Ataxia-telangiectasia (A-T) is a human autosomal recessive disorder characterized by neuronal degeneration as well as many other physiological and somatic defects. ATM (A-T, mutated), the gene mutated in A-T, encodes a 370 kDa protein kinase. ATM knockout mouse models (ATM(-/-)) show growth retardation, infertility, neurological dysfunction, defects in T-lymphocytes, and extreme sensitivity to ionizing radiation. We have recently established multiple ATM(+/-) breeding pairs and discovered that all ATM(-/-) offspring exhibit a nonpigmented section of tail, usually at or near the tip. To our knowledge, this is the first time that a phenotype of nonpigmented tail has been reported in ATM(-/-) knockout mice. We believe that the sections of nonpigmented tail of 129S6/SvEvTac-ATM(tm1Awb)/J mice provide a novel phenotypic marker for research using this ATM knockout mouse model. Results from histochemistry and immunoblotting analysis further demonstrate that while melanocyte precursors or melanoblasts are present in the nonpigmented tail tissue of ATM(-/-) mice, they fail to differentiate fully into mature melanocytes. The potential connection between this phenotype and other clinical symptoms caused by ATM deficiency, such as progressive neuronal degeneration, is discussed in this article.
共济失调毛细血管扩张症（A-T）是一种人类常染色体隐性疾病，其特征为神经元退化以及许多其他生理和躯体缺陷。ATM（A-T突变）基因在A-T中发生突变，编码一种370 kDa的蛋白激酶。ATM基因敲除小鼠模型（ATM(-/-)）表现出生长迟缓、不育、神经功能障碍、T淋巴细胞缺陷以及对电离辐射极度敏感。我们最近建立了多对ATM(+/-)繁殖对，并发现所有ATM(-/-)后代的尾巴都有一段无色素区域，通常在尾巴尖端或其附近。据我们所知，这是首次在ATM(-/-)基因敲除小鼠中报道无色素尾巴的表型。我们认为，129S6/SvEvTac-ATM(tm1Awb)/J小鼠的无色素尾巴区域为使用这种ATM基因敲除小鼠模型的研究提供了一种新的表型标记。组织化学和免疫印迹分析结果进一步表明，虽然ATM(-/-)小鼠无色素尾巴组织中存在黑素细胞前体或成黑素细胞，但它们未能完全分化为成熟的黑素细胞。本文讨论了这种表型与ATM缺乏引起的其他临床症状（如进行性神经元退化）之间的潜在联系。
